title: TNF induces the expression of the sialyltransferase ST3Gal IV in human bronchial mucosa via MSK1/2 protein kinases and increases FliD/sialyl-Lewis(x)-mediated adhesion of Pseudomonas aeruginosa.
abstract: We have shown previously that the pro-inflammatory cytokine TNF (tumour necrosis factor) could drive sLe(x) (sialyl-Lewis(x)) biosynthesis through the up-regulation of the BX transcript isoform of the ST3GAL4 (ST3 β-galactoside α-2,3-sialyltransferase 4) sialyltransferase gene in lung epithelial cells and human bronchial mucosa. In the present study, we show that the TNF-induced up-regulation of the ST3GAL4 BX transcript is mediated by MSK1/2 (mitogen- and stress-activated kinase 1/2) through the ERK (extracellular-signal-regulated kinase) and p38 MAPK (mitogen-activated protein kinase) pathways, and increases sLe(x) expression on high-molecular-mass glycoproteins in inflamed airway epithelium. We also show that the TNF-induced sLe(x) expression increases the adhesion of the Pseudomonas aeruginosa PAO1 and PAK strains to lung epithelial cells in a FliD-dependent manner. These results suggest that ERK and p38 MAPK, and the downstream kinase MSK1/2, should be considered as potential targets to hamper inflammation, bronchial mucin glycosylation changes and P. aeruginosa binding in the lung of patients suffering from lung diseases such as chronic bronchitis or cystic fibrosis.
authors.affiliation: *Université Lille Nord de France, Lille 1, UGSF (Unité de Glycobiologie Structurale et Fonctionnelle), CNRS (Centre National de la Recherche Scientifique), UMR 8576, 59650 Villeneuve d'Ascq, France.
authors.forename: Florent
authors.initials: F
authors.lastname: Colomb
authors.forename: Olivier
authors.initials: O
authors.lastname: Vidal
authors.forename: Marie
authors.initials: M
authors.lastname: Bobowski
authors.forename: Marie-Ange
authors.initials: MA
authors.lastname: Krzewinski-Recchi
authors.forename: Anne
authors.initials: A
authors.lastname: Harduin-Lepers
authors.forename: Eric
authors.initials: E
authors.lastname: Mensier
authors.forename: Sophie
authors.initials: S
authors.lastname: Jaillard
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Lafitte
authors.forename: Philippe
authors.initials: P
authors.lastname: Delannoy
authors.forename: Sophie
authors.initials: S
authors.lastname: Groux-Degroote
mesh_terms: D001422:Bacterial Adhesion / Q000187:drug effects*; D001426:Bacterial Proteins / Q000502:physiology; D001980:Bronchi / Q000187:drug effects / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D009844:Oligosaccharides / Q000502:physiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000502:physiology; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000378:metabolism; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000502:physiology*; D000080506:Sialyl Lewis X Antigen; D012799:Sialyltransferases / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase
chemical_list: D001426:Bacterial Proteins; D009844:Oligosaccharides; D000080506:Sialyl Lewis X Antigen; D014409:Tumor Necrosis Factor-alpha; C076733:FlaD protein, Bacteria; D012799:Sialyltransferases; C115634:RPS6KA4 protein, human; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C116919:mitogen and stress-activated protein kinase 1; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase